FDA Investigational Device Exemption (IDE) Application Process

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The FDA Investigational Device Exemption (IDE) regulations distinguish between significant and non-significant risk devices, and the level of risk of a device will be subject to different levels of regulatory control. Non-significant risk device studies only require Institutional Review Board (IRB) approval prior to the study's start. Sponsors of significant risk devices are required to submit an IDE application and receive FDA and IRB approval before clinical studies can begin. In this article, we share the FDA's IDE application process and common problems.

Introduction of IDE

An IDE allows the use of an investigational device in a clinical study to collect safety and efficacy data. Clinical studies are typically used to support PMAs, and only a small percentage of 510(k)s require clinical data to support a device application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices.

Unless exempt, all clinical evaluations of investigational devices must have an approved IDE prior to the start of the study. The circumstances under which an IDE may be exempt are set forth in § 812.2(c) of the IDE regulations. This includes diagnostic devices if their sponsors meet the applicable requirements in § 809.10(c) and the tests satisfy the following conditions:

It is non-intrusive
It does not require an invasive sampling procedure that poses a significant risk
It is not designed or intended to introduce energy into the subject's body
It is not to be used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure

List of Materials for IDE Applications

Sponsors of research on significant risk devices (e.g., pacemakers) that may pose a serious threat to the health and safety of subjects must submit a complete IDE application to FDA. There are no pre-printed forms for an IDE application, but the IDE application must include certain required information. The sponsor must demonstrate the following in the application:

There is reason to believe that the importance of the benefits expected to be derived from the proposed research and the knowledge to be gained by the subjects will outweigh the risk of harm to the subjects from the research
The research is scientifically sound
There is reason to believe that the device proposed for use is effective

The sponsor cannot begin a significant risk device study until it has received FDA and IRB approval. A valid electronic copy of the IDE application is usually required, and the application must include the following, in order (§ 812.20)

1. The sponsor's name and address
2. Pre-study report (§ 812.27)

The pre-study report must include reports of all preclinical, animal, and laboratory testing of the device. It should be comprehensive and sufficient to justify the proposed study. Specific elements of the report must be included:

A bibliography of all publications relevant to the evaluation of the safety and efficacy of the device, both adverse and positive
Copies of all published and unpublished adverse information
Copies of other significant publications required by the IRB or FDA
A summary of all other unpublished information, whether negative or supportive, relevant to the evaluation of the safety and effectiveness of the device

If non-clinical laboratory data are provided, a statement that such studies have been conducted in accordance with Good Laboratory Practice (GLP) regulations in 21 CFR Part 58. If the study was not conducted in accordance with GLP regulations, briefly describe the reasons for noncompliance

3. Research plan (§ 812.25)

The research plan should include the following in order:

Purpose: The name and intended use of the device and the objectives and duration of the study

Protocol: A written protocol describing the proposed methodology and an analysis of the protocol to demonstrate its scientific soundness

Risk analysis: Description and analysis of all increased risks to the study population and how these risks will be minimized, rationale for the study and description of the patient population, including number, age, gender, and status

Device description: Description of each significant component, ingredient, characteristic, and principle of operation of the device, as well as any anticipated changes in the device during the study period

Monitoring procedures: The sponsor's written procedures for overseeing the study and the name and address of each monitor

Additional records and reports: Description of any study records or reports other than those required by Part G of the IDE Regulatory

4. Description of the methods, facilities, and controls used to manufacture, process, package, store, and install the equipment
5. Example of an agreement signed by the investigator(s) and a list of the names and addresses of all investigators. See § 812.43 for information that must be included in a written agreement.
6. Evidence that all investigators have signed the protocol. The list of Investigators includes all Investigators participating in the study, and new Investigators will sign the agreement before joining the study
7. List of the names, addresses, and chairpersons of all IRBs that have been or will be asked to review the study, and evidence of IRB action on the study
8. The names and addresses of all institutions that may conduct portions of the study
9. The amount charged for the equipment, if any, and an explanation of why the sale does not constitute commercialization
10. Please note that an environmental assessment is no longer required under 21 CFR 25.40 and a request for a categorical exclusion is no longer required under 21 CFR 25.30 or 25.34
11. The copy of all labelling for the device
12. Copies of all informed consent forms and all relevant informational materials provided to subjects as required by 21 CFR 50, Protection of Human Subjects
13. Any other relevant information requested by FDA for review of the IDE application, and information previously submitted to FDA under part 812 can be incorporated by reference

IDE Submission Format

To facilitate the processing of IDE applications, FDA makes the following recommendations:

Clearly and conspicuously identify whether the submission is an original IDE application or a supplemental submission to an application, and clearly identify the FDA-assigned file number (e.g., G960000) and the reason for the submission (e.g., amendment, supplement, or report), as well as the type of submission (e.g., response to FDA's approval letter with conditions, change to protocol, annual report, etc.).
Submit valid electronic copies in accordance with the guidance document entitled "eCopy Medical Device Submissions".
Do not combine IDEs, PMAs, and 510(k)s and they must be submitted separately.
Only the IDE sponsor may amend, supplement, or submit an IDE report unless the IDE sponsor authorizes another person to submit information on the sponsor's behalf in writing.

Common Problems with IDE Applications

Sponsors should ensure that the device, all preclinical testing, and the study plan are described and a strong rationale is provided for initiating a clinical trial. Sponsors should avoid submitting an IDE application too early.

There are three common areas where IDE applications are often deficient: inadequate pre-study reports, inadequate study plans, and inadequate/incomplete design for manufacture.

Common deficiencies in pre-study reports

The pre-study report must include reports of all prior clinical, animal, and laboratory testing of the device. It should be comprehensive and adequate to justify the proposed study. If a specific type of pre-study was not performed (e.g., no animal testing or no clinical studies), the pre-study report should provide justification.

1. Laboratory studies

Inadequate description of methods
Inadequate or no summary/conclusion
Conclusions are not supported by data

2. Report of animal studies

No rationale for animal selection
No scientific basis for selection of the number of animals
Inappropriate duration or follow-up
Failure to address adherence to nonclinical study GLP 21 CFR 58

3. Reports of previous publications

Incomplete search
Does not include copies of relevant publications
Omission of adverse information
Failure to identify relevant sections or information and summarize

Common deficiencies in research programs

Failure to clearly formulate or define research objectives
Inadequate description of the protocol
Failure to identify all risks
Research plans include elements that expose research subjects to unacceptable risks
Failure to establish adequate monitoring procedures
Inadequate informed consent

Common deficiencies in design and manufacturing

Design: Inadequate characterization or description of the equipment and its operation due to inadequacy or omission, including:

Equipment design/engineering drawings
Fundamentals of equipment design
Device and performance specifications
Material description (including biocompatibility information)
Functional description - how the device and/or components/subsystems work together to achieve the desired function
Validation testing of subsystems and master systems

Manufacturing: Inadequate or missing description of controls used to ensure that the device is produced consistently and as designed

Proregulations provides comprehensive IDE application services for medical device companies. If you are interested in our services or need more details, please contact us.